The need to regain public trust in the safety and quality of drugs and biotech therapies has been a prominent theme of FDA officials in recent weeks. They stress the importance of identifying critical factors early in the biomedical research process that may affect product quality and have issued new policies to achieve those goals. At the same time, the regulators have taken steps to show they can be tough enforcers of manufacturing rules and willing to pull questionable therapies off the market.

SEEKING PHARMACOGENOMIC DATA
One FDA initiative encourages manufacturers to provide genomic data to the agency, either as part of a market application or through a new voluntary process, to encourage pharmacogenomic research leading to more "personalized" medicine. FDA notes that voluntary data submissions can help both regulatory and industry scientists keep abreast of new developments in this area.

Last month, FDA released a concept paper on the co-development of new drugs and diagnostics that identify patients who could benefit or suffer from a new therapy. This followed a March guidance explaining how manufacturers may submit pharmacogenomic data to FDA. The agency maintains the information will not affect the review of formal applications for new drugs and biologics, but it will be examined separately by a new interdisciplinary pharmacogenomics review group. Despite these reassurances, pharma and biotech companies are concerned that FDA will expand requirements for including pharmacogenomic information in applications as reviewers and researchers learn more about the value of this information.

This guidance specifically addresses only pharmacogenomics data related to ensuring appropriate clinical testing and use of certain drugs — and not genetic or genomic techniques used for biological product characterization or quality control, a topic FDA plans to address in future guidance documents. The current guidance also does not cover data resulting from proteomic or metabolomic analysis techniques, although it notes that manufacturers may submit such data to FDA for consideration and discussion under the voluntary submission process. The pharmacogenomics guidance, along with additional information on submitting data to FDA is available at
http://www.fda.gov/cder/genomics/default.htm.

Scientists from industry, academia, NIH, and FDA discussed the documents and their implications at a three-day conference designed to translate three years of deliberations into practical proposals for using pharmacogneomics in drug development. FDA Acting Deputy Director Janet Woodcock opened the meeting, co-sponsored by FDA, industry, and the DIA, by outlining the "real imperative" for improving the current wasteful, uninformative system for testing drug candidates. She urged a shift to research methods that use biomarkers to predict drug side effects and benefits, more specifically. Success in this area can address the current "affordability and access" healthcare crisis, she said, as well as the need for a more agile process to produce medical countermeasures in response to public health emergencies.

Although FDA's policies emphasize that broader assessment of pharmacogenomics data offers potential benefits in clinical trial design and drug development, the advent of more individualized medicines may bring significant changes to the biotech industry. A recent report by Price- WaterhouseCoopers on "Personalized Medicine: The Emerging Pharmacogenomics Revolution" predicts an eventual erosion of the current blockbuster drug business model, a development that offers significant opportunities for smaller life sciences companies. Initial pharmacogenomic breakthroughs are most likely to occur in oncology, and developing and launching new drugs in this area will require further changes in regulatory and clinical practices to incorporate genetic testing as part of patient diagnosis and treatment.

RISKS AND RESEARCH
FDA also published final guidances that describe ways to minimize drug risk through full collection of safety data prior to approval and more sophisticated management of risky medical products on the market. Although focused on clinical trial design and post-market risk management, the guidances present a number of issues important to biotech manufacturers.

The guidance on premarket risk assessment, which outlines additional testing and study approaches likely to enhance a sponsor's understanding of product safety concerns, could affect demand for clinical supplies and encourage expanded clinical assessment of proposed packaging and product design. Another guidance describes the development and use of risk minimization action plans or RiskMAPS to assure that patients safely use certain high-risk products. While emphasizing that only a limited number of products will warrant such efforts, FDA notes it has authority to require product recalls, safety alerts, seizures, or injunctions to prevent the possibility of "serious risks to the public health" if risk minimization efforts fail.